The Pediatric Brain Tumor Foundation Institute at Duke was founded in 2003, under the leadership of Darell D. Bigner, MD, PhD. The Institute is devoted exclusively to pediatric brain tumor research. Brain tumors are one of the deadliest forms of childhood cancer, and there are more than 28,000 children living in the U.S. today who have been diagnosed with a primary brain tumor. The main goal of the Institute is to develop innovative and less invasive clinical treatments for these children.

The Pediatric Brain Tumor Foundation awarded a $6 million grant to Duke in 2003, and gave a second $6 million, six-year grant in 2008. In 2015, the PBTF awarded Duke $1 million under the direction of John H. Sampson, MD, PhD, MBA, MHSc. In order to generate more knowledge of pediatric brain tumors, the PBTF Institute at Duke collaborates extensively with the two other PBTF Institutes: the University of California, San Francisco and the Hospital for Sick Children in Toronto.

Pediatric Brain Tumor Foundation

Mission

The Pediatric Brain Tumor Foundation works to eliminate the challenges of childhood brain tumors. Its mission is to cure the kids. The foundation funds research into the cause of and cure for childhood brain tumors, works to increase public awareness about the disease, and provides financial, educational, and emotional support to children and families affected by brain tumors.

Research

The Pediatric Brain Tumor Foundation has funded innovative research initiatives on behalf of children with brain tumors for more than three decades. Its national signature fundraising events are the Ride for Kids motorcycle charity ride and the Starry Night 8.5K walk/run. These events have helped the PBTF become the world’s largest non-profit source of funding for research into childhood brain tumors.

Support for Families

The PBTF offers hope to brain tumor survivors and their families in many ways. Its resources include a toll-free help line, educational conferences and brochures, online support groups, emergency financial assistance, and college scholarships for survivors. For more information, please call (800) 253-6530 or email familysupport@curethekids.org.

Project 1: Development of a Peptide Vaccine for Diffuse Intrinsic Pontine Glioma

Goals: Diffuse intrinsic pontine gliomas (DIPGs) are the leading cause of death for children with brain tumors. These tumors are refractory to chemotherapy, are treated solely with focal radiation as standard of care (SOC), and have median overall survival (OS) of less than a year. In contrast to the non-specific and toxic SOC radiotherapy regimen for DIPG, immunotherapy promises an exquisitely precise approach. However, immunotherapy is limited in this role due to a lack of consistently expressed and tumor specific antigens. Recently, point mutations were discovered in histone H.3 (H3F3A) and H3.1 (HIST1H3B) at amino acid 27 replacing lysine with methionine in almost 80% of DIPGs and 22% of pediatric glioblastomas. This provides a highly conserved and tumor specific mutation, H3.3K27M, in 60% of DIPGs. We propose to address the question of whether targeting the H3.3K27M mutation with optimized peptide vaccination can serve as a novel immunotherapy against a preclinical DIPG model. Our primary research objectives are to: (1) maximize 15mer PEP-H3.3 immunogenicity through adjuvant selection, (2) optimize vaccination timing in combination with SOC radiation therapy in an H3.3K27M-positive murine model of DIPG6, and (3) perform studies of PEP-H3.3 for an investigational new drug (IND) application to the FDA. The goals of this research are to develop a completely novel and absolutely tumor-specific treatment that will harmlessly infiltrate normal brain while selectively killing tissue. The development of such a therapy would alter the current paradigm of treatment for DIPG and provide a novel therapy for an incurable pediatric tumor.

Core Summary: Despite the advances in surgical and imaging techniques, we still face many obstacles when treating children with brain tumors. Some of the impediments stem from the extensive infiltration of tumor cells, their invasion into normal brain tissue, and resistance to standard radiation and chemotherapy. However, the major obstacle to successfully treating pediatric brain tumors results from a clear lack of understanding of the underlying biology of this disease. The heterogeneity within pediatric brain tumors and the fact that they vary in histological appearance, cell biology, and the tumor markers they produce only intensifies the problem. To help better understand this disease there is a clear need to develop patient-derived brain tumor models that recapitulate the human disease and provide in vivo and in vitro models that help researchers in the following manner: to study genetic alterations that result in brain tumor initiation, progression, and maintenance; and to help identify relevant therapeutic targets and provide appropriate preclinical modes in which to test novel therapeutic agents.

Core Summary: The projects in the Pediatric Brain Tumor Foundation Institute (PBTFI) at Duke rely on human tissue samples, the vast majority of which are derived from the Duke Operating Rooms and Clinics, and all of which are procured, assessed, and distributed through this Biorepository Core. This core continues to benefit from existing funding from the NIH, the Preston Robert Tisch (PRT) family, and the Pediatric Brain Tumor Foundation (PBTF) and provides for light microscopic and molecular diagnostic analysis on all banked specimens so that researchers have access to histologically and genotypically characterized aliquots of tumors. These are indirectly linked with Duke Hospital Pathology reports that include a common profile of diagnostic, proliferative, phenotypic, and genotypic analyses. Our close association with the Biostatistics and Information Systems Shared Resources of the Duke Cancer Institute assures that we have integrated tissue bank/clinical data informatics databases to handle data collection and distribution needs for clinical trials and tracking of specimens. Using this infrastructure, customized databases to support each individual project can be parsed from a master database based on a large variety of descriptors characterizing each specimen. Database administration, development of web-based strategies, and the integration of genetic data will come from our Biorepository collaborators. The mission of the Biorepository is to maintain a tissue bank with integrated histologic and molecular diagnostic data on all stored tissues that will provide the diagnostic assessments proposed for the pre-clinical and clinical studies comprising the projects of the Institute.